Radiotherapy to the head and neck region leads to severe side effects in the oral cavity but knowledge about severity and onset is scarce among oncology nurses in a radiotherapy department. The aim was to test the Oral Assessment Guide for reliability and validity for patients receiving radiotherapy to the head and neck region. A prospective design with repeated assessments was selected. Thirty-six outpatients admitted to the department for radiotherapy to the head and neck region were included. In connection with the treatment session, the oral cavity was examined every second day by a nurse and once a week by an oncologist. The results were documented on separate forms. All patients showed alterations in the oral cavity and side effects started early during the first week of treatment. The result from inter-rater reliability showed a high concordance in all categories (>71%). Cohen's kappa (k) showed good agreement for voice, swallow and saliva and moderate for lips, tongue, mucous membranes, gums and teeth/dentures. The association, the sensitivity, between dose of radiation and side effects was weak or moderate and the acceptability with patients and staff was generally good.